A Randomized Controlled Study Assessing Convalescent Immunoglobulins versus Convalescent Plasma for Hospitalized COVID-19 Patients.

BACKGROUND: It is unknown whether convalescent immunoglobulins (cIgG) are better than convalescent plasma (CP) for COVID-19 patients. METHODS: In this randomized trial we assigned high risk COVID-19 with ≤10 days of symptoms, to receive cIgG or CP. The primary endpoint was improvement on day 14 according to the WHO scale. Secondary endpoints were survival on day 14, and improvement, survival, and percent of ventilated patients on day 28 and treatment response in unvaccinated and vaccinated patients. RESULTS: 319 patients were included; 166 received cIgG, and 153 CP. Median age was 64-66 years. 112 patients (67.5%) in the cIgG and 103 patients (67.3%) in the CP group reached the primary endpoint. Difference between groups was 0.1 (95%CI -10.1-10.4, p=0.026), failing to reach non-inferiority. More patients receiving cIgG improved by day 28 [136 patients (81.9%) and 108 patients (70.6%), respectively, 95% CI 1.9-20.7, p<0.001, for superiority p=0.018)]. 17 patients in the cIgG group (10.2%) and 25 patients (16.3%) in the CP group required mechanical ventilation (p=0.136). 16 (9.6%) and 23 (15%) patients respectively died (p=0.172). More unvaccinated patients improved by day 28 in the cIgG group (84.1% vs. 66.1%, p<0.024) and survival was better in the cIgG group (89.9% vs. 77.4% p=0.066). CONCLUSIONS: cIgG failed to reach the primary non-inferiority endpoint on day 14 but was superior to CP on day 28. Survival and improvement by day 28 in unvaccinated patients treated with cIgG were better. In the face of new variants, cIgG is a viable option for treating COVID-19. TRIAL REGISTRATION NUMBER: My Trials MOH_2021-01-14_009667.

Predictors of reinfection with pre-Omicron and Omicron variants of concern among individuals who recovered from COVID-19 in the first year of the pandemic.

OBJECTIVES: The predictors of SARS-CoV-2 reinfection are unclear. We examined predictors of reinfection with pre-Omicron and Omicron variants among COVID-19-recovered individuals. METHODS: Randomly selected COVID-19-recovered patients (N = 1004) who donated convalescent plasma during 2020 were interviewed between August 2021 and March 2022 regarding COVID-19 vaccination and laboratory-proven reinfection. The sera from 224 (22.3%) participants were tested for antispike (anti-S) immunoglobulin G and neutralizing antibodies. RESULTS: The participants' median age was 31.1 years (78.6% males). The overall reinfection incidence rate was 12.8%; 2.7% versus 21.6% for the pre-Omicron (mostly Delta) versus Omicron variants. Negative associations were found between fever during the first illness and pre-Omicron reinfection: relative risk 0.29 (95% confidence interval 0.09-0.94), high anti-N level at first illness and Omicron reinfection: 0.53 (0.33-0.85), and overall reinfection: 0.56 (0.37-0.84), as well as between subsequent COVID-19 vaccination with the BNT162b2 vaccine and pre-Omicron 0.15 (0.07-0.32), Omicron 0.48 (0.25-0.45), and overall reinfections 0.38 (0.25-0.58). These variables significantly correlated with immunoglobulin G anti-S follow-up levels. High pre-existing anti-S binding and neutralizing antibody levels against the SARS-CoV-2 Wuhan and Alpha strains predicted protection against Omicron reinfections. CONCLUSION: Strong immune responses after the first COVID-19 infection and subsequent vaccination with the BNT162b2 vaccine provided cross-protection against reinfections with the Delta and Omicron variants.

Estimated Infection and Vaccine Induced SARS-CoV-2 Seroprevalence in Israel among Adults, January 2020-July 2021.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerged in Israel in February 2020 and spread from then. In December 2020, the FDA approved an emergency use authorization of the Pfizer-BioNTech vaccine, and on 20 December, an immunization campaign began among adults in Israel. We characterized seropositivity for IgG anti-spike antibodies against SARS-CoV-2 between January 2020 and July 2021, before and after the introduction of the vaccine in Israel among adults. We tested 9520 serum samples, collected between January 2020 and July 2021. Between January and August 2020, seropositivity rates were lower than 5.0%; this rate increased from September 2020 (6.3%) to April 2021 (84.9%) and reached 79.1% in July 2021. Between January and December 2020, low socio-economic rank was an independent, significant correlate for seropositivity. Between January and July 2021, the 40.00-64.99-year-old age group, Jews and others, and residents of the Northern district were significantly more likely to be seropositive. Our findings indicate a slow, non-significant increase in the seropositivity rate to SARS-CoV-2 between January and December 2020. Following the introduction of the Pfizer-BioNTech vaccine in Israel, a significant increase in seropositivity was observed from January until April 2021, with stable rates thereafter, up to July 2021.

SARS-CoV-2 IgG Antibody Levels in Women with IBD Vaccinated during Pregnancy.

INTRODUCTION: Regulatory agencies supported vaccination of pregnant women with SARS-CoV-2 mRNA vaccines, including patients with IBD. No data exist regarding these vaccines in IBD during pregnancy. AIM: To assess the serologic response to two doses of the mRNA SARS-CoV-2 BNT162b2 vaccine in pregnant women with IBD vaccinated during pregnancy, compared to that of pregnant women without IBD, and non-pregnant women with IBD. METHODS: Anti-spike antibody levels were assessed in all women and in cord blood of consenting women. RESULTS: From December 2020 to December 2021, 139 women were assessed: pregnant with IBD-36, pregnant without IBD-61, and not pregnant with IBD-42. Antibodies were assessed in cords of two and nine newborns of women with and without IBD, respectively. Mean gestational ages at administration of the second vaccine doses were 22.0 weeks in IBD and 23.2 weeks in non-IBD, respectively. Mean (SD) duration from the second vaccine dose to serology analysis in pregnant women with IBD, without IBD, and in non-pregnant women with IBD was 10.6 (4.9), 16.4 (6.3), and 4.3 (1.0) weeks, respectively. All women mounted a serologic response. In multivariable analysis, no correlation was found between the specific group and antibody levels. In both pregnancy groups, an inverse correlation between antibody levels and the interval from the second vaccine dose was demonstrated. Cord blood antibody levels exceeded maternal levels in women with and without IBD. CONCLUSION: All patients with IBD mounted a serologic response. The interval between vaccine administration to serology assessment was the most important factor determining antibody levels. A third vaccine dose should be considered in pregnant women with IBD vaccinated at early stages of pregnancy.

Anti-TNFα Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases.

Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNFα and 57 treated with anti-TNFα) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNFα had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNFα. Importantly, all seronegative subjects were patients with IBD; of those, >90% were treated with anti-TNFα. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients.

Effectiveness of BNT162b2 mRNA Coronavirus Disease 2019 (COVID-19) Vaccine Against Acquisition of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Among Healthcare Workers in Long-Term Care Facilities: A Prospective Cohort Study.

BACKGROUND: We assessed vaccine effectiveness (VE) of BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) acquisition among healthcare workers (HCWs) of long-term care facilities (LTCFs). METHODS: This prospective study, in the framework of the "Senior Shield" program in Israel, included routine weekly nasopharyngeal SARS-CoV-2 RT-PCR testing from all LTCF HCWs since July 2020. All residents and 75% of HCWs were immunized between December 2020 and January 2021. The analysis was limited to HCWs adhering to routine testing. Fully vaccinated (14+ days after second dose; n = 6960) and unvaccinated (n = 2202) HCWs were simultaneously followed until SARS-CoV-2 acquisition or end of follow-up, 11 April 2021. Hazard ratios (HRs) for vaccination versus no vaccination were calculated (Cox proportional hazards regression models, adjusting for sociodemographics and residential-area COVID-19 incidence). VE was calculated as (1- HR) × 100. RT-PCR cycle threshold (Ct) values were compared between vaccinated and unvaccinated HCWs. RESULTS: At >14 days post-second dose, 40 vaccinated HCWs acquired SARS-CoV-2 (median follow-up, 66 days; cumulative incidence, 0.6%) versus 84 unvaccinated HCWs (median follow-up, 43 days; cumulative incidence, 5.1%) (HR, .11; 95% CI, .07-.17; unadjusted VE, 89%; 95% CI, 83-93%). Adjusted VE >7 and >14 days post-second dose were similar. The median PCR Ct targeting the ORF1ab gene among 20 vaccinated and 40 unvaccinated HCWs was 32.0 versus 26.7, respectively (P value  = .008). CONCLUSIONS: VE following 2 doses of BNT162b2 against SARS-CoV-2 acquisition in LTCF HCWs was high. The lower viral loads among SARS-CoV-2-positive HCWs suggest further reduction in transmission.

The Incidence of SARS-CoV-2 Reinfection in Persons With Naturally Acquired Immunity With and Without Subsequent Receipt of a Single Dose of BNT162b2 Vaccine : A Retrospective Cohort Study.

BACKGROUND: There is insufficient evidence regarding the magnitude and durability of protection conferred by a combined effect of naturally acquired immunity after SARS-CoV-2 infection and vaccine-induced immunity. OBJECTIVE: To compare the incidence rate of SARS-CoV-2 reinfection in previously infected persons to that of previously infected persons who subsequently received a single dose of BNT162b2 messenger RNA vaccine. DESIGN: A retrospective cohort study emulating a randomized controlled target trial through a series of nested trials. SETTING: Nationally centralized database of Maccabi Healthcare Services, Israel. PARTICIPANTS: Persons with documented SARS-CoV-2 infection who did not receive subsequent SARS-CoV-2 vaccination were compared with persons with documented SARS-CoV-2 infection who received a single dose of the BNT162b2 vaccine at least 3 months after infection. INTERVENTION: Forty-one randomized controlled trials were emulated, in which 107 413 Maccabi Healthcare Services' members aged 16 years and older were eligible for at least 1 trial. MEASUREMENTS: SARS-CoV-2-related outcomes of infection, symptomatic disease, hospitalization, and death, between 2 March and 13 December 2021. RESULTS: A statistically significant decreased risk (hazard ratio, 0.18 [95% CI, 0.15 to 0.20]) for reinfection was found among persons who were previously infected and then vaccinated versus those who were previously infected but remained unvaccinated. In addition, there was a decreased risk for symptomatic disease (hazard ratio, 0.24 [CI, 0.20 to 0.29]) among previously infected and vaccinated persons compared with those who were not vaccinated after infection. No COVID-19-related mortality cases were found. LIMITATION: Hybrid protection against non-Delta variants could not be inferred. CONCLUSION: Persons previously infected with SARS-CoV-2 gained additional protection against reinfection and COVID-19 from a subsequent single dose of the BNT162b2 vaccine. Nonetheless, even without a subsequent vaccination, reinfection appeared relatively rare. PRIMARY FUNDING SOURCE: None.

Association of BNT162b2 Vaccine Third Dose Receipt With Incidence of SARS-CoV-2 Infection, COVID-19-Related Hospitalization, and Death Among Residents of Long-term Care Facilities, August to October 2021.

Importance: COVID-19 vaccine might be less immunogenic and effective among residents of long-term care facilities (LTCFs). Objective: To examine the association of BNT162b2 third dose (first booster dose) with overall SARS-CoV-2 infection, COVID-19 hospitalizations, and mortality among LTCF residents during a nationwide surge of the Delta variant in Israel. Design, Setting, and Participants: This observational cohort study conducted nationwide COVID-19 surveillance in LTCFs in Israel between August and October 2021. Participants were residents of LTCFs aged 60 years or older. Exposures: Vaccination with the third dose of BNT162b2 vaccine vs receipt of 2 doses at least 5 months earlier, based on self-preference and choice. Main Outcomes and Measures: The cumulative incidences of reverse transcription-polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection, COVID-19 hospitalizations, and COVID-19-related deaths more than 7 days after vaccination with the third dose were compared between the groups using Kaplan-Meier curves. Hazard ratios (HRs) and 95% CIs were obtained using multivariable Cox regression models. Results: Among 18 611 residents included in the analysis, 12 715 (68.3%) were female, 463 (2.5%) were from the Arab population, 16 976 (91.2%) were from the general Jewish population, and 618 (3.3%) were from the ultraorthodox Jewish population; the mean (SD) age was 81.1 (9.2) years; 16 082 residents received their first booster dose (third dose) and 2529 were vaccinated with 2 doses at least 5 months earlier. The median (IQR) follow-up durations were 66 (60-70) days among 3-dose recipients and 56 (53-62) days among 2-dose-only recipients; 107 residents had SARS-CoV-2 infection after 7 days following vaccination with the booster dose compared with 185 among the 2-dose only group (cumulative incidence: 0.7% vs 7.5%; adjusted HR, 0.11 [95% CI, 0.07-0.15]). The respective adjusted HRs were 0.07 (95% CI, 0.03-0.14) and 0.10 (95% CI, 0.04-0.24) for the associations of vaccination with the third dose with hospitalization for mild-to-moderate COVID-19 and severe illness. Five COVID-19-related deaths occurred among the third dose vaccinees during the follow-up period compared with 22 among the 2-dose-only vaccinees (cumulative rate: 0.04% vs 0.9%; adjusted HR, 0.04 [95% CI, 0.009-0.16]). Conclusions and Relevance: This cohort study found significant inverse associations between vaccination with the third dose of the BNT162b2 vaccine with overall SARS-CoV-2 infection, COVID-19 hospitalizations, severe disease, and COVID-19-related deaths among LTCF residents during a massive surge caused by the Delta variant in Israel.

Association of Receipt of the Fourth BNT162b2 Dose With Omicron Infection and COVID-19 Hospitalizations Among Residents of Long-term Care Facilities.

Importance: The administration of a fourth BNT162b2 COVID-19 vaccine dose was approved in Israel in December 2021 for individuals 60 years or older who were vaccinated with a third dose 4 months previously or earlier to control the substantial surge of the SARS-CoV-2 Omicron variant. Nonetheless, the association between receipt of the fourth dose and protection against infection remains elusive. Objective: To determine the association of the fourth BNT162b2 dose with protection against SARS-CoV-2-related infections, hospitalizations, and deaths during the Omicron surge in long-term care facility (LTCF) residents. Design, Setting, and Participants: This prospective cohort study was conducted in Israel between January 10 and March 31, 2022 and included LTCF residents 60 years or older. Exposures: Vaccination with the fourth dose of BNT162b2 vs 3 doses that were administered 4 months previously or earlier. Main Outcomes and Measures: Cumulative incidences of SARS-CoV-2 infections, hospitalizations, and deaths during the Omicron surge. The follow-up was initiated more than 7 days after receipt of the fourth dose, which was matched to the follow-up initiation date of those who had received 3 doses of vaccine in each facility. We obtained hazard ratios and 95% confidence intervals from multivariable Cox regression models. Results: The data of 43 775 residents (mean [SD] age, 80.1 [9.4] years; 29 679 women [67.8%]) were analyzed, of whom 24 088 (55.0%) and 19 687 (45.0%) received the fourth and third dose (4 months previously or earlier), respectively. The median follow-up time was 73 days (4-dose group: IQR, 6 days; 3-dose group: IQR, 56 days). More than 7 days postvaccination with the fourth dose, SARS-CoV-2 infection was detected among 4058 fourth-dose vs 4370 third-dose recipients (cumulative incidence, 17.6% vs 24.9%). The corresponding incidences of hospitalizations for mild-to-moderate COVID-19, severe illness, and mortality were 0.9% and 2.8%, 0.5% and 1.5%, and 0.2% and 0.5%, respectively. The adjusted protections were 34% (95% CI, 30%-37%), 64% (95% CI, 56%-71%), and 67% (95% CI, 57%-75%) against overall infection, hospitalizations for mild-to-moderate illness, and severe illness, respectively, and 72% (95% CI, 57%-83%) against related deaths. Conclusions and Relevance: The results of this cohort study suggest that receipt of a fourth BNT162b2 dose conferred high protection against COVID-19 hospitalizations and deaths among LTCF residents during a substantial Omicron variant surge, but protection was modest against infection. These findings are relevant to the control of COVID-19 pandemic globally, especially among the population of LTCFs.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Naturally Acquired Immunity versus Vaccine-induced Immunity, Reinfections versus Breakthrough Infections: A Retrospective Cohort Study.

BACKGROUND: Waning of protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) conferred by 2 doses of the BNT162b2 vaccine begins shortly after inoculation and becomes substantial within 4 months. With that, the impact of prior infection on incident SARS-CoV-2 reinfection is unclear. Therefore, we examined the long-term protection of naturally acquired immunity (protection conferred by previous infection) compared to vaccine-induced immunity. METHODS: A retrospective observational study of 124 500 persons, compared 2 groups: (1) SARS-CoV-2-naive individuals who received a 2-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, and (2) previously infected individuals who have not been vaccinated. Two multivariate logistic regression models were applied, evaluating four SARS-CoV-2-related outcomes-infection, symptomatic disease (coronavirus disease 2019 [COVID-19]), hospitalization, and death-between 1 June and 14 August 2021, when the Delta variant was dominant in Israel. RESULTS: SARS-CoV-2-naive vaccinees had a 13.06-fold (95% confidence interval [CI], 8.08-21.11) increased risk for breakthrough infection with the Delta variant compared to unvaccinated-previously-infected individuals, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant for symptomatic disease as well. When allowing the infection to occur at any time between March 2020 and February 2021, evidence of waning naturally acquired immunity was demonstrated, although SARS-CoV-2 naive vaccinees still had a 5.96-fold (95% CI: 4.85-7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI: 5.51-9.21) increased risk for symptomatic disease. CONCLUSIONS: Naturally acquired immunity confers stronger protection against infection and symptomatic disease caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 2-dose vaccine-indued immunity.

Lower Serologic Response to COVID-19 mRNA Vaccine in Patients With Inflammatory Bowel Diseases Treated With Anti-TNFα.

BACKGROUND & AIM: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)α biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA-Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs). METHODS: Prospective, controlled, multicenter Israeli study. Subjects enrolled received 2 BNT162b2 (Pfizer/BioNTech) doses. Anti-spike antibody levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinally. RESULTS: Overall, 258 subjects: 185 IBD (67 treated with anti-TNFα, 118 non-anti-TNFα), and 73 HCs. After the first vaccine dose, all HCs were seropositive, whereas ∼7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose, all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (both P < .001). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (P < .03; P < .0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-spike levels. Infection rate (∼2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2. CONCLUSIONS: In this prospective study in patients with IBD stratified according to treatment, all patients mounted serologic response to 2 doses of BNT162b2; however, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered.

Sero-Prevalence and Sero-Incidence of Antibodies to SARS-CoV-2 in Health Care Workers in Israel, Prior to Mass COVID-19 Vaccination.

Objectives: This study aims to examine the prevalence and risk factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sero-positivity in health care workers (HCWs), a main risk group, and assess the sero-incidence of SARS-CoV-2 infection between the first and second waves of coronavirus disease 2019 (COVID-19) in Israel. Methods: A longitudinal study was conducted among 874 HCWs from nine hospitals. Demographics, health information, and blood samples were obtained at baseline (first wave-April-May 2020) and at follow-up (n = 373) (second wave-September-November 2020). Sero-positivity was determined based on the detection of total antibodies to the nucleocapsid antigen of SARS-CoV-2, using electro-chemiluminescence immunoassay (Elecsys® Anti-SARS-CoV-2, Roche Diagnostics, Rotkreuz, Switzerland). Results: The sero-prevalence of SARS-CoV-2 antibodies was 1.1% [95% confidence intervals (CI) 0.6-2.1] at baseline and 8.3% (95% CI 5.9-11.6) at follow-up. The sero-conversion of SARS-CoV-2 serum antibody was 6.9% (95% CI 4.7-9.9) during the study period. The increase in SARS-CoV-2 sero-prevalence paralleled the rise in PCR-confirmed SARS-CoV-2 infections among the HCWs across the country. The likelihood of SARS-CoV-2 sero-prevalence was higher in males vs. females [odds ratio (OR) 2.52 (95% CI 1.05-6.06)] and in nurses vs. physicians [OR 4.26 (95% CI 1.08-16.77)] and was associated with being quarantined due to exposure to COVID-19 patients [OR 3.54 (95% CI 1.58-7.89)] and having a positive PCR result [OR 109.5 (95% CI 23.88-502.12)]. Conclusions: A significant increase in the risk of SARS-CoV-2 infection was found among HCWs between the first and second waves of COVID-19 in Israel. Nonetheless, the sero-prevalence of SARS-CoV-2 antibodies remains low, similar to the general population. Our findings reinforce the rigorous infection control policy, including quarantine, and utilization of personal protective equipment that should be continued together with COVID-19 immunization in HCWs and the general population.

Assessment of Effectiveness of 1 Dose of BNT162b2 Vaccine for SARS-CoV-2 Infection 13 to 24 Days After Immunization.

Importance: The BNT162b2 vaccine showed high efficacy against COVID-19 in a phase III randomized clinical trial. A vaccine effectiveness evaluation in a real-world setting is needed. Objective: To assess the short-term effectiveness of the first dose of the BNT162b2-vaccine against SARS-CoV-2 infection 13 to 24 days after immunization in a real-world setting. Design, Setting, and Participants: This comparative effectiveness study used data from a 2.6 million-member state-mandated health care system in Israel. Participants included all individuals aged 16 years and older who received 1 dose of the BNT162b2 vaccine between December 19, 2020, and January 15, 2021. Data were analyzed in March 2021. Exposure: Receipt of 1 dose of the BNT162b2 vaccine. Main Outcomes and Measures: Information was collected regarding medical history and positive SARS-CoV-2 polymerase chain reaction test and COVID-19 symptoms from 1 day after first vaccine to January 17, 2021. Daily and cumulative infection rates in days 13 to 24 were compared with days 1 to 12 after the first dose using Kaplan-Meier survival analysis and generalized linear models. Results: Data for 503 875 individuals (mean [SD] age, 59.7 [14.7] years; 263 228 [52.4%] women) were analyzed, of whom 351 897 had follow-up data for days 13 to 24. The cumulative incidence of SARS-CoV-2 infection was 2484 individuals (0.57%) during days 1 through 12 and 614 individuals (0.27%) in days 13 through 24. The weighted mean (SE) daily incidence of SARS-CoV-2 infection in days 1 through 12 was 43.41 (12.07) infections per 100 000 population and 21.08 (6.16) infections per 100 000 population in days 13 through 24, a relative risk reduction (RRR) of 51.4% (95% CI, 16.3%-71.8%). The decrease in incidence was evident from day 18 after the first dose. Similar RRRs were calculated in individuals aged 60 years or older (44.5%; 95% CI, 4.1%-67.9%), those younger than 60 years (50.2%; 95% CI, 14.1%-71.2%), women (50.0%; 95% CI, 13.5%-71.0%), and men (52.1%; 95% CI, 17.3%-72.2%). Findings were similar in subpopulations (eg, ultraorthodox Jewish: RRR, 53.5% [95% CI, 19.2%-73.2%]) and patients with various comorbidities (eg, cardiovascular diseases: RRR, 47.2% [95% CI, 7.8%-69.8%]). Vaccine effectiveness against symptomatic COVID-19 was 54.4% (95% CI, 21.4%-73.6%). Conclusions and Relevance: In this comparative effectiveness study of a single dose of the BNT162b2 vaccine, results were comparable to that of the phase III randomized clinical trial.

A nationwide analysis of population group differences in the COVID-19 epidemic in Israel, February 2020-February 2021.

BACKGROUND: Social inequalities affect the COVID-19 burden and vaccine uptake. The aim of this study was to explore inequalities in the incidence and mortality rate of SARS-CoV-2 infection and vaccine uptake in various sociodemographic and population group strata in Israel. METHODS: We analysed nationwide publicly available, aggregated data on PCR-confirmed SARS-CoV-2 infections and COVID-19 deaths between March 2020 and February 2021, as well as the first three months of COVID-19 immunisation according to sociodemographics, including population group and residential socioeconomic status (SES). We computed incidence and mortality rates of COVID-19. Comparisons between towns with predominantly Arab, ultra-Orthodox Jewish (the minorities), general Jewish populations, and according to SES, were conducted using generalised linear models with negative binomial distribution. FINDINGS: Overall, 774,030 individuals had SARS-CoV-2 infection (cumulative incidence 84•5 per 1,000 persons) and 5687 COVID-19 patients had died (mortality rate 62•8 per 100,000 persons). The highest mortality rate was found amongst the elderly. Most (>75%) individuals aged 60 years or above have been vaccinated with BNT162b2 vaccine. The risk of SARS-CoV-2 infection was higher in towns with predominantly Arab and ultra-Orthodox Jewish populations than in the general Jewish population, and in low SES communities. COVID-19 mortality rate was highest amongst Arabs. Conversely, vaccine uptake was lower amongst Arab and ultra-Orthodox Jewish populations and low SES communities. INTERPRETATION: Ethnic and religious minorities and low SES communities experience substantial COVID-19 burden, and have lower vaccine uptake, even in a society with universal accessibility to healthcare. Quantifying these inequalities is fundamental towards reducing these gaps, which imposes a designated apportion of resources to adequately control the pandemic. FUNDING: No external funding was available for this study.

The Effectiveness of the Two-Dose BNT162b2 Vaccine: Analysis of Real-World Data.

BACKGROUND: Coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines were shown to be highly efficacious in preventing the disease in randomized controlled trials; nonetheless, evidence on the real-world effectiveness of this vaccine is limited. Study objective was to evaluate the effectiveness of BNT162b2 vaccine in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related hospitalization and mortality. METHODS: This historical cohort study included members of a large health provider in Israel that were vaccinated with at least 1 dose of BNT162b2. The primary outcome was incidence rate of a SARS-CoV-2 infection confirmed with real-time polymerase chain reaction (rt-PCR), between 7 and 27 days after second dose (protection-period), as compared to days 1-7 after the first dose, where no protection by the vaccine is assumed (reference-period). RESULTS: Data of 1 178 597 individuals vaccinated with BNT162b2 were analyzed (mean age 47.7 years [SD = 18.1], 48.4% males) of whom 872 454 (74.0%) reached the protection period. Overall, 4514 infections occurred during the reference period compared to 728 during the protection period, yielding a weighted mean daily incidence of 54.8 per 100 000 (95% confidence interval [CI]: 26.1-115.0 per 100 000) and 5.4 per 100 000 (95% CI: 3.5-8.4 per 100 000), respectively. The vaccine effectiveness in preventing infection was 90% (95% CI: 79%-95%) and 94% (95% CI: 88%-97%) against COVID-19. Among immunosuppressed patients, vaccine effectiveness against infection was 71% (95% CI: 37%-87%). The adjusted hazard ratios for hospitalization in those infected were 0.82 (95% CI: .36-1.88), 0.45 (95% CI: .23-.90), and 0.56 (95% CI: .36-.89) in the age groups 16-44, 45-64. and ≥75 years, respectively. CONCLUSIONS: The effectiveness of the BNT162b2 vaccine is comparable to the one reported in the phase III clinical trial.

A Significant Decrease in the Incidence of Shigellosis in Israel during COVID-19 Pandemic.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes COVID-19 and is mostly person-to-person transmitted through respiratory droplets. The implications of the strategies implemented to prevent COVID-19 transmission on other infectious diseases are unclear. We aimed to appraise trends in the incidence of salmonellosis, shigellosis and campylobacteriosis in Israel during COVID-19 pandemic. Positive stool samples for Salmonella, Shigella and Campylobacter are reported on a monthly basis to the Israel Center for Disease Control from sentinel laboratories, within the framework of a surveillance network of bacterial culture-proven enteric diseases. Age-adjusted incidence rates per 100,000 of shigellosis, salmonellosis and campylobacteriosis were calculated. Mean rates before and after the local onset of COVID-19 pandemic in Israel were compared and Relative Risk Reduction (RRR) was calculated. Joinpoint was used to evaluate secular trends. The mean age-adjusted incidence rate of shigellosis in March-July 2020 was lower than the rate observed in March-July 2018-2019 (RRR = 86.6%), but also decreased for salmonellosis (RRR = 33.0%) and campylobacteriosis (RRR = 30.0%). Using Joinpoint we have shown that the decrease observed for shigellosis was significantly sharper (Annual Percent Change (APC) = -77.7) between February 2020 and May 2020 than for salmonellosis (APC = -14.0) between July 2019 and April 2020 and for campylobacteriosis (APC = -1.1) between January 2018 and July 2020. The preventive measures applied to reduce transmission of COVID-19, including social distancing and hand washing, were ecologically associated with a decreased risk of bacterial enteric diseases in Israel. The association was strongest for shigellosis, a disease that is mostly person-to-person transmitted, as compared to salmonellosis and campylobacteriosis which are mostly foodborne transmitted.